The goal of this proposal is to obtain, at autopsy, brain tissue from individuals who have been clinically well-characterized during life and to prepare and maintain the tissue in a manner that is optimal for the research studies. Brain tissue will be obtained from individuals who are neurologically normal, or diagnosed as "probable" Alzheimer's disease (AD), possible AD, and non-AD dementia (Pick's disease, Multi-infarct Dementia, etc.). All of the individuals for whom we have consents will have been evaluated thoroughly at the UCI AD clinic. This includes a group of control individuals who are participants in a Foster Grandparent Program and who have been evaluated for the past four years in a study examining physical and mental indices of age-related decline. The autopsy protocol is designed to provide fresh frozen tissue for biochemical and molecular studies and fixed tissue for neuropathological evaluation and for immunochemistry and in situ hybridization One hemisphere of the brain is dissected, with the various regions snap-frozen and stored at -70oC. Regions can also be placed into fixative, depending on the specific needs of the research studies. The frozen sections include the entire rostral-caudal extent of the hippocampus. The opposite hemisphere is sliced into 7 mm coronal sections, with alternating sections fixed in 4% paraformaldehyde or frozen between prechilled (-40oC) aluminum plates. Areas for neuropathological evaluation are removed from the fixed sections and are paraffin-embedded. The remaining tissues are equilibrated in 18% sucrose in phosphate-buffered saline (RNase free), frozen, and stored at - 70oC. This tissue is used for immunochemical and in situ hybridization studies. The Human Brain Tissue Repository will also provide neuropathological assessment on tissues adjacent to those used for biochemical studies.